Adolescence is a developmental period during which individuals engage in risk-taking behavior and are likely to initiate use of alcohol or other drugs. Past research suggests a strong correlation between early age of onset of alcohol use and a heightened vulnerability to addiction later in life. Adolescence is also a time of considerable neuromaturation, particularly in frontal brain regions thought to subserve higher level cognition, such as decision making and inhibition. Heavy alcohol use during these critical periods of brain development may permanently disrupt the course of maturation, resulting in long-term deficits in these functions and thereby increasing the risk of subsequent substance use behavior. The proposed R01 project is designed to prospectively and longitudinally examine the influence of developmental stage on the effects of alcohol on adolescent cognition, brain functioning, and brain structure, using neuroimaging and neuropsychological testing techniques. This project will examine neuropsychological performance during tests of executive functioning, brain functioning during executive and risk taking fMRI tasks, brain structure in prefrontal and limbic regions, and frontostriatal white matter integrity in 250 at-risk, non-using 12-14-year-old youth (based on family history of alcoholism). We hypothesize that youth who drink in adolescence will show abnormalities on these measures compared to developmentally-matched non-drinking youth, and that youth who initiate heavy drinking earlier in puberty will show greater abnormalities than teens that initiate heavy drinking later in development. This prospective study will answer critical questions about how developmental timing of adolescent heavy alcohol use initiation affects the developing brain. PUBLIC HEALTH RELEVANCE: Studies show that the adolescent brain may be particularly vulnerable to alcohol's neurotoxic effects, and that earlier use is associated with greater subsequent risk of addictive behaviors. Despite this, alcohol use is very common among adolescence. Understanding the impact of early alcohol use on the developing adolescent brain will facilitate the creation of interventions aimed at reducing alcohol drinking behaviors that are targeted at specific age and risk groups.